Carbazic acid derivatives, process for their preparation and compositions containing the same

ABSTRACT

The invention relates to new carbazic acid derivatives, a process for the preparation thereof and compositions--particularly feed additives and animal feeds--containing the same. The new compounds according to the invention correspond to the formula (I) 
     
         R.sup.1 ═N--NH--COOR.sup.3                             (I) 
    
     wherein R 1  stands for a C 7-12  cycloalkylidene group, an indanylidene group or a group of the formula (IX) ##STR1## wherein A represents a phenyl group optionally carrying one or more identical or different substituents selected from the group consisting of halo, nitro, hydroxy, C 1-4  alkoxy, C 1-4  alkyl, amino or C 1-4  alkoxycarbonylhydrazino; phenyl-(C 1-4  alkyl), C 1-16  alkyl, C 3-7  cycloalkyl or indolyl, or a C 3  -C 6  cycloalkyl group substituted by a C 3  -C 6  cycloalkyl group; R 2  denotes a hydrogen atom, a C 1-16  alkyl or a C 3-7  cycloalkyl group; and R 3  represents a C 1-4  alkyl group.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of copending Ser. No.573,586 filed Jan. 24, 1984, now U.S. Pat. No. 4,570,002, which is acontinuation-in-part of Ser. No. 491,035 filed May 3, 1983, nowabandoned.

This invention relates to new carbazic acid derivatives, a process forthe preparation thereof and compositions--particularly feed additivesand animal feeds--containing the same.

According to the present invention there are provided new carbazic acidderivatives of the formula (I)

    R.sup.1 ═N--NH--COOR.sup.3                             (I)

wherein

R¹ stands for a C₇₋₁₂ cycloalkylidene group, an indanylidene group or agroup of the formula (IX) ##STR2## wherein A represents a phenyl groupwhich can have one or more identical or different substituents selectedfrom the group consisting of halo, nitro, hydroxy, C₁₋₄ alkoxy, C₁₋₄alkyl, amino or C₁₋₄ alkoxycarbonylhydrazino; a phenyl-(C₁₋₄ alkyl), aC₁₋₁₆ alkyl, a C₃₋₇ cycloalkyl, an indolyl group, or a C₃ -C₆ cycloalkylgroup substituted by C₃ -C₆ cycloalkyl;

R² denotes a hydrogen atom, a C₁₋₁₆ alkyl or a C₃₋₇ cycloalkyl group;and

R³ represents a C₁₋₄ alkyl group.

The term "alkyl group" used in the specification and claims refers tostraight-chained or branched saturated aliphatic hydrocarbyl groupscontaining the given number of carbon atoms (e.g. methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, n-hexyl, n-dodecyl,n-hexadecyl). The term "alkoxy group" relates to straight-chained orbranched alkylether groups containing the given number of carbon atoms(e.g. methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy group, etc.). Theterm "phenyl-(C₁₋₄ alkyl) group" represents preferably benzyl orβ-phenylethyl. The "C₃₋₇ cycloalkyl group" may be cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

The phenyl group at the symbol A may carry one or more nitro, hydroxy,C₁₋₄ alkoxy, C₁₋₄ alkyl, amino or C₁₋₄ alkoxycarbonylhydrazinosubstituents. When the phenyl group carries several substituents, thesemay be identical or different.

Preferred representatives of the compounds of the formula (I) are thosewherein R³ is a methyl group.

A particularly preferred representative of the compounds of the formula(I) is the methyl-[3-(o-aminobenzylidene)]-carbazate.

Further preferred compounds of the formula (I) are those disclosed inthe Examples.

According to a further feature of the invention there is provided aprocess for the preparation of compounds having the formula (I),characterized by (a) reacting a carbonyl compound of the formula (II)wherein B represents an oxygen or a sulfur atom and R¹ is as definedabove, or a reactive derivative thereof with a hydrazine derivative ofthe formula (III)

    H.sub.2 N--NH--COOR.sup.3                                  (III)

wherein R³ is as defined above, or with a reactive derivative thereofformed on the amino group, or (b) reacting a carbonyl compound of theformula (II), wherein R¹ and B are as defined above, with hydrazine ofthe formula (IV)

    H.sub.2 N--NH.sub.2                                        (IV)

or with an acid addition salt thereof, and reacting the thus-obtainedcompound of the formula (V)

    R.sup.1 ═N--NH.sub.2                                   (V)

wherein R¹ is as defined above, after or without isolation, with acompound of the formula (VI)

    Hlg--COOR.sup.2                                            (VI)

wherein Hlg represents halogen and R³ has the above defined meanings.

According to method (a) of the invention a carbonyl compound of theformula (II) is reacted with a hydrazine derivative of the formula(III). It is preferable to start with a carbonyl compound of the formula(II), wherein B stands for oxygen. Preferably equimolar amounts of thecompounds of the formulae (II) and (III) are reacted, but one of thestarting substances may be used in a slight excess as well. The reactionmay be performed in an inert organic solvent. For this purpose any inertsolvent dissolving properly the starting substances is suitable. Asreaction medium, preferably aromatic hydrocarbons (e.g. benzene,toluene, xylene) or alcohols (e.g. methanol, ethanol, isopropanol) mayserve. The reaction is preferably carried out under heating, at atemperature between about 40° C. and the boiling point of the reacitonmixture. One proceeds preferably at about the boiling point of thereaction mixture.

The reaction is preferably carried out in the presence of a strong acid.Preferably acetic acid may serve for this purpose.

The compounds of the formula (I) can be isolated from the reactionmixture by known methods (e.g. crystallization or evaporation).

Instead of the carbonyl compounds of the formula (II) and/or thehydrazine derivatives of the formula (III) the reactive derivativesthereof can also be used. Among the reactive derivatives of the carbonylcompounds of the formula (II) preferably the ketales of the formula(VII) are mentioned ##STR3## wherein R⁵ and R⁴ each represent a loweralkyl group or form together a lower alkylene group, and R¹ is asdefined above. These ketales may be preferably dimethyl, diethyl orethylene ketales. The reaction may be effected at a temperature betweenabout 20° C. and 200° C. an an inert solvent. As reaction medium,preferably aromatic hydrocarbons (e.g. benzene, toluene or xylene) areused. The reaction is preferably carried out in the presence ofcatalytic amounts of a strong acid. For this purpose e.g. hydrogenchloride, hydrogen bromide or p-toluenesulfonic acid may serve.

Instead of the compounds of the formula (III) the reactive derivativesthereof formed on the amino group may be used as well. These compoundscorrespond to the formula (VIII) ##STR4## wherein R⁷ representshydrogen, lower alkyl or phenyl,

R⁶ denotes hydrogen or lower alkyl, or

R⁶ and R⁷ form, together with the adjacent carbon atoms to which theyare attached, a C₃₋₇ cycloalkylidene ring, with the proviso that atleast one of R⁶ and R⁷ is other than hydrogen. The reaction can beperformed at a temperature between about 20° C. and 200° C., in an inertsolvent. As reaction medium, organic solvents inert toward the reactionand dissolving the starting substances (e.g. alcohols, such as methanolor ethanol; esters, such as ethyl acetate) may be used. The reaction iscarried out in the presence of catalytic amounts of a strong acid. Ascatalyst hydrogen chloride, hydrogen bromide, sulfuric, phosphoric,trifluoroacetic or p-toluenesulfonic acid can be used.

According to method (b) of the invention a compound of the formula (II)is reacted with hydrazine of the formula (IV) or with an acid additionsalt thereof, and the compound of the formula (V) thus obtained isreacted with a compound of the formula (VI), after or without isolation.The first step of the reaction is performed at a temperature betweenroom temperature and 60° C., in an inert solvent. As reaction medium,preferably alcohols (e.g. methanol or ethanol) are used.

Instead of the hydrazine of the formula (V), optionally the acidaddition salt (e.g. the hydrochloride or sulfate) thereof is applied.One proceeds preferably by reacting a compound of the formula (II) withhydrazine dihydrochloride in the presence of one molar equivalent of abase. As the base inorganic bases (e.g. alkali hydroxides, carbonates orhydrogen carbonates, preferably sodium hydroxide, potassium carbonate orpotassium hydrogen carbonate) or organic bases (e.g. triethylamine) canbe used.

The thus-obtained compound of the formula (V) is reacted with thehaloformate of the formula (VI) after or--preferably--without isolation.It is preferable to use compounds of the formula (VI), wherein Hlgstands for chlorine. The reaction may be carried out in the presence ofan acid binding agent. For this purpose the inorganic or organic baseslisted in the previous paragraph may serve.

The compounds of the formula (I) with acidic character can be convertedinto the corresponding salt. The salt formation is carried out in aknown way. The alkali salts (e.g. sodium or potassium salts), thealkaline-earth salts (e.g. calcium or magnesium salts) and the saltsformed with biologically acceptable organic bases (such astriethylamine, dimethylamine, dimethylaniline) are particularlypreferred.

The starting substances used for the synthesis according to theinvention are in part commercial products or compounds known from theliterature or can be prepared by methods known per se.

The new compounds of the formula (I) can be used in animal husbandry dueto their weight gain increasing properties.

The weight gain increasing effect of the new compounds of the formula(I) is shown in the following tests. (A) Young pigs are used as testanimals. Each animal group consists of 6 pigs and each test with 6 pigsare repeated 3 times. The fodder contains 50 mg/kg of test compound. Theanimals are fed under identical conditions and all the animal groupsreceive the same amount of fodder having the same composition. Thus theanimals of the reference group are fed with the same fodder except thatthe fodder contains Flavomycine in the place of the compound of theformula (I). The animals of the control group receive a fodder to whichneither a test compound of the formula (I) nor Flavomycine is added.

The weight gain is registered daily and the average daily weight gain iscalculated by the following formula:

    (Average daily weight gain in the test group/Average daily weight gain in the control group)×100

The amount of the fodder eaten by the animals of the test group ismultiplied by the weight gain obtained in the said test group. Thequotient obtained for the test group is related to the quotientcalculated for the control group. This value expresses the amount offodder required to obtain 1 kg of weight gain.

The test results thus obtained are summarized in Table (I) B. The testaccording to paragraph (A) is repeated on animal groups consisting of 50pigs. The feeding period is 60 days and the test compound is added in adose of 50 mg/kg. The results obtained are compared to those achievedwith a fodder containing Flavomycine under the same conditions. Theresults obtained with Flavomycine are regarded as 100% and the testresults obtained are summarized in Table II.

                  TABLE I                                                         ______________________________________                                                               Amount of fodder required                                         Average daily                                                                             to obtain 1 kg of weight                                          weight gain gain, related to the con-                              Test compound                                                                            g/day       trols                                                  ______________________________________                                        Example 4  463          82%                                                   Flavomycine                                                                              345          95%                                                   Control group                                                                            336         100%                                                   ______________________________________                                    

                  TABLE II                                                        ______________________________________                                                                        Amount of fodder pro-                                       daily weight gain ducing 1 kg of weight                         Test  Aver-   expressed as % of gain expressed as % of                        com-  age     the Flavomycine   the Flavomycine                               pound g/day   group        kg   group                                         ______________________________________                                         6    546     121          1.80 77.6                                          21    541     120          2.07 90.0                                          22    503       111.7      2.00 86.5                                          Flavo-                                                                              450       100.0      2.32 100.0                                         mycine                                                                        ______________________________________                                    

It appears from the above data that the weight gain of the animals fedwith a fodder containing the compounds of the invention is significantlygreater than that of the pigs of the control grop. At the same time thesame weight gain can be achieved with a considerably smaller amount offodder when a compound of the formula (I) is incorporated into theanimal feed. This is proof of an improved fodder utilization.

The compound of Example 15 ensures a weight gain of 5.4% in chickens incomparison to the weight of chickens in a control group.

The toxicity of the compounds of the formula (I) on domestic animals isso low that the compounds are practically atoxic.

According to a further feature of the invention there are providedcompositions for use in animals husbandry comprising as activeingredient an amount of 1 ppm to 85% by weight of a compound of theformula (I), wherein R¹ and R³ are as defined above, or a biologicallyacceptable salt thereof in admixture with suitable inert solid or liquidcarriers or diluents.

The compositions of the present invention may be particularly fodderadditives and fodders comprising as active ingredient an amount of 1 ppmto 85% by weight of a compound of the formula (I), wherein R^(i) and R³are as defined above, or a biologically acceptable salt thereof inadmixture with suitable edible solid or liquid carriers or diluents.

According to a further feature of the invention there is provided aprocess for the preparation of fodder additives and fodders, whichcomprises admixing a compound of the formula (I), wherein R¹ and R³ areas defined above, or a biologically acceptable salt thereof with asuitable edible solid or liquid carrier or diluent and additivegenerally used in the production of fodder additives and fodders.

As carrier or diluent any substance of vegetable or animal originapplicable in the feeding of animals or serving as fodder can be used.For this purpose e.g. wheat, rice, maize, soybean, alfalfa, barley,oats, rye can be used in appropriate forms (grits, groats, meal, bran,etc.), furthermore fish meal, meat meal, bone meal or mixtures thereofcan be used as well. One may advantageously use a fiber-free green plantfodder concentrate with high protein content (e.g. VEPEX®).

As additives e.g. silicic acid, wetting agents, antioxidants, starch,dicalcium phosphate, calcium carbonate, sorbic acid, etc. can be used.As wetting agent e.g. non-toxic oils, preferably soybean oil, maize oilor mineral oil can be applied. Various alkylene glycols can also be usedas wetting agent. The starch used may be wheat, maize or potato starch.

The fodder additives and concentrates may contain usual vitamins (e.g.vitamin A, B₁, B₂, B₃, B₆, B₁₂, E, K) and trace elements (e.g. Mn, Fe,Zn, Cu, I), too.

The active ingredient content of the compositions may vary within wideranges. The fodder additives and concentrates may contain about 5-80% byweight, preferably about 10-80% by weight of the active ingredient ofthe formula (I). The active ingredient content of the animal foddersready for use may be about 1-400 ppm, preferably about 10-100 ppm.

The fodder additives and concentrates are diluted with suitable foddercomponents or are incorporated into suitable animal feeds to provideanimal feeds ready for use.

The fodder according to the present invention can be used for theincrease of weight gain and improvement of feed utilization of variousdomestic animals, such as pigs, lambs, cattle and poultry, particularlypigs.

Further details of the present invention are to be found in thefollowing Examples of non-limiting character:

EXAMPLE 1 Preparation of methyl-[3-(α-isopropylbenzylidene)]-carbazate

To a solution of 44.46 g (0.3 moles) of isobutyrophenone in 200 ml ofmethanol 3 ml of acetic acid and 27 g of methyl carbazate are added. Thereaction mixture is boiled in a flask equipped with a reflux condenser,then clarified and evaporated in vacuo to half of its original volume.The residue is cooled and the separated tallow-like product is filteredoff. Yield: 64.2 g (97.3%) M.p.: 78°-80° C. The product can berecrystallized from petrol.

EXAMPLE 2 Preparation of methyl-[3-(3'-indolylmethylene)]-carbazate

36.29 g (0.25 moles) of indole-3-aldehyde are dissolved in 300 ml ofmethanol. Then 3 ml of acetic acid and 0.25 moles of methyl carbazateare added to the solution. The reaction mixture is boiled for one hourin a flask equipped with a reflux condenser, then clarified. 50 ml ofwater are added to the filtrate and the separated pink crystals arefiltered off. 51.5 g of the desired compound are obtained. Yield: 94.9%.M.p.: 144°-145° C.

EXAMPLE 3 Preparation of methyl-[3-(1-indanylidene)]-carbazate

To a solution of 39.65 g (0.3 moles) of 1-indanone in 300 ml of methanol3 ml of acetic acid and 27 g (0.3 moles) of methyl carbazate are added.The reaction mixture is boiled in a flask equipped with a refluxcondenser for one hour, then clarified with bone coal, filtered and thefiltrate is cooled with icy water. 43.7 g of the desired compound areobtained in the form of white crystals. M.p.: 155°-156° C.

The mother liquor is evaporated in vacuo to about one-fourth of itsoriginal volume. In this way another 12.3 g of the desired compound areobtained. Yield: 91.5%.

EXAMPLE 4 Preparation of methyl-[-3(o-aminobenzylidene)]-carbazate

One proceeds as described in Example 3, with the difference that 36.35 g(0.3 moles) of 2-aminobenzaldehyde are used as the starting substance.50 g of the desired compound are obtained. Yield: 86.35%. M.p.:149°-150° C.

EXAMPLE 5 Preparation of methyl-[3-cyclooctylidene]-carbazate

One proceeds as described in Example 1, with the difference that 37.86 g(0.3 moles) of cyclooctanone are used as the starting substance. 49 g ofthe desired compound are obtained. Yield: 82.5%. M.p.: 93°-94° C.

EXAMPLE 6 Preparation of methyl-[3-(p-nitrobenzylidene)]-carbazate

One proceeds as described in Example 3, with the difference that 45.34 g(0.3 moles) of p-nitrobenzaldehyde are used as the starting substance.61.5 g of the desired compound are obtained. Yield: 91.9%. M.p.:212°-213° C.

EXAMPLE 7 Preparation of methyl-[3-(1'-phenylhexadecylidene)]-carbazate

47.48 g (0.15 moles) of palmitophenone and 13.5 g (0.15 moles) of methylcarbazate are reacted in the way described in Example 1. 47.3 g (81.3%)of the desired compound are obtained. Yield: 81.3%. M.p.: 68°-69° C.

EXAMPLE 8 Preparation of methyl-[3-(1'-benzylpropylidene)]-carbazate

One proceeds as described in Example 1, with the difference that 44.46 g(0.3 moles) of ethylbenzyl ketone are used as the starting substance. 66g of the desired compound are obtained. Yield: 99.9%. M.p.: 80° C.

EXAMPLE 9 Preparation ofmethyl-[3-(2',4'-dihydroxybenzylidene)]-carbazate

To a solution of 34.5 g (0.25 moles) of 2,4-dihydroxybenzaldehyde in 300ml of methanol 3 ml of acetic acid and 22.5 g (0.25 moles) of methylcarbazate are added. The reaction mixture is boiled for 2 hours in aflask equipped with a reflux condenser, then clarified with bonecharcoal, filtered and the filtrate is cooled. 49.2 g of the desiredcompound are obtained. Yield: 93.4%. M.p.: 205° C.

EXAMPLE 10 Preparation ofmethyl-[3-(3',4',5'-trimethoxybenzylidene)]-carbazate

30.86 g (0.2 moles) of 2,4,5-trimethoxybenzaldehyde and 18 g (0.2 moles)of methyl carbazate are reacted in the way described in Example 1. Thedesired compound separates in the form of white crystals. Yield: 48.6 g(86%). M.p.: 140°-141° C.

EXAMPLE 11 Preparation of methyl-[3-(1'-ethylpropylidene)]-carbazate

One proceeds as described in Example 9, with the difference that 34.4 g(0.4 moles) of diethyl ketone are used as the starting substance. 57.15g (90.4%) of the desired compound are obtained in the form of whitecrystals. M.p.: 66°-67° C. (after recrystallization from petrol).

EXAMPLE 12 Preparation ofmethyl-[3-(3'-ethoxy-4'-hydroxybenzylidene)]-carbazate

One proceeds as described in Example 9, with the difference that 41.6 g(0.25 moles) of 3-ethoxy-4-hydroxy-benzaldehyde are used as the startingsubstance. 56.3 g of the desired compound are obtained in the form ofwhite crystals. Yield: 94.6%. M.p.: 172°-173° C.

EXAMPLE 13 Preparation of methyl-[3-(1'-methylpentylidene)]-carbazate

One proceeds in the way described in Example 9, with the difference that34.25 g (0.3 moles) of ethyl-(n-butyl)-ketone are used as the startingsubstance. 35.4 g of the desired compound are obtained. Yield: 63.4%.M.p.: 67°-68° C.

EXAMPLE 14 Preparation of methyl-[3-(cycloheptylidene)]-carbazate

One proceeds in the way described in Example 1, with the difference that33.6 g (0.3 moles) of cycloheptanone are used as the starting substance.49.25 g of the desired compound are obtained in the form of whitecrystals. Yield: 89.1%. M.p.: 75° C.

EXAMPLE 15 Preparation ofmethyl-[3-(α-ethyl)-p-hydroxybenzylidene]-carbazate

One proceeds in the way described in Example 1, with the difference that37.54 g (0.25 moles) of p-hydroxypropiophenone are used as startingsubstance. 43.8 g of the desired compound are obtained. Yield: 78.85%.M.p.: 167° C.

EXAMPLE 16 Preparation of methyl-(3-cyclododecylidene)-carbazate

One proceeds in the way described in Example 9, with the difference that45.6 g (0.25 moles) of cyclododecanone are used as the startingsubstance. 52.5 g of the desired compound are obtained in the form ofwhite crystals. Yield: 83.2%. M.p.: 141°-142° C.

EXAMPLE 17 Preparation of methyl-(3-cyclohexylidene)-carbazate

To a solution of 11.2 g (0.1 mole) of cyclohexanone in 100 ml ofmethanol 2 ml of acetic acid and 9.0 g (0.1 mole) of methyl carbazateare added. The reaction mixture is boiled in a flask equipped with areflux condenser for 2 hours, then clarified, filtered and the filtrateis evaporated in vacuo. 15.6 g of the desired compound are obtained inthe form of white crystals. Yield: 84.8%. M.p.: 103° C.

EXAMPLE 18 Preparation ofmethyl-[3-(4'-hydroxy-3'-nitrobenzylidene)]-carbazate

One proceeds in the way described in Example 3, with the diffrence that33.4 g (0.2 moles) of 4-hydroxy-3-nitrobenzaldehyde are used as thestarting substance. 41.65 g of the desired compound are obtained. M.p.:175°-176° C. Yield: 87.1%.

EXAMPLE 19 Preparation of methyl-[3-(2'-nitrobenzylidene)]-carbazate

One proceeds in the way described in Example 3, with the difference that30.2 g (0.2 moles) of 2-nitrobenzaldehyde are used as the startingsubstance. 36.85 g of the desired compound are obtained in the form ofpale yellow crystals. Yield: 82.6%. M.p.: 152° C.

EXAMPLE 20 Preparation ofmethyl-[3-(4',5'-dimethoxy-2'-nitrobenzylidene)]-carbazate

One proceeds in the way described in Example 9, with the difference that52.8 g (0.25 moles) of 2-nitro-4,5-dimethoxybenzaldehyde are used asstarting substance. 57.6 g of the desired compound (yellow product) areobtained. Yield: 81.5%. M.p.: 230°-231° C.

EXAMPLE 21 Preparation ofmethyl[3-(3'-chloro-5'-nitrobenzylidene)]-carbazate

One proceeds in the way described in Example 3 with the difference that3-chloro-5-nitrobenzaldehyde is used as the starting material.

EXAMPLE 22 Preparation ofmethyl[3-(α-ethyl)-p-chlorobenzylidene]-carbazate

One proceeds in the way described in Example 1 with the difference thatp-chloropropiophenone is used as the starting material.

EXAMPLE 23 Preparation ofmethyl[3-(α-cyclopropyl-4'-methoxybenzylidene]-carbazate

To a solution of 17.6 g (0.1 mole) of cyclopropyl 4-methoxyphenyl ketonein 100 ml of methanol 3 ml of acetic acid and thereafter 9.0 g (0.1mole) methyl carbazate are added. The reaction mixture is boiled for 5hours, then clarified and hot filtered. The filtrate is evaporated invacuo, treated with 10 ml of ether and the separated white crystals arerecovered by filtering. 18.3 g (73.7%) of the title compound areobtained. M.p.: 114°-115° C.

EXAMPLE 24 Preparation ofmethyl[3-(4'-chloro-3'-nitrobenzylidene)]-carbazate

One proceeds in the way described in Example 1 with the difference that18.55 g (0.1 mole) of 4-chloro-3-nitrobenzaldehyde and 9 g (0.1 mole) ofmethyl carbazate are used as starting substances. 23.8 g (92.4%) of thetitle compound are obtained. M.p.: 190° C.

EXAMPLE 25 Preparation ofmethyl[3-(2'-cyclohexylcyclohexylidene)]-carbazate

35.66 g (0.2 moles) of 2-cyclohexylcyclohexanone are dissolved in 250 mlof methanol, 18 g (0.2 moles) of methyl carbazate and 3 ml of aceticacid are added. After 2 hours of reflux the reaction mixture isclarified and then evaporated. White crystals separate from the obtainedoil. After slurrying with benzene 46.6 g (87.2%) of the title productare obtained. M.p.: 130° C.

EXAMPLE 26 Preparation ofmethyl[3-(2',4'-dichlorobenzylidene)]-carbazate

One proceeds in the way described in Example 1 with the difference that43.75 g (0.25 mole) of 2,4-dichlorobenzaldehyde and 22.5 g (0.25 mole)of methyl carbazate are used as the starting substances. 53.2 g (86.2%)of the title compound are obtained. M.p.: 156°-157° C.

EXAMPLE 27 Preparation ofmethyl[3-(3',4'-dichlorobenzylidene)]-carbazate

From 43.75 g (0.25 moles) of 3,4-dichlorobenzaldehyde and 22.5 g (0.25mole) of methyl carbazate 57.25 g (92.7%) of the title compound areprepared. M.p. 154°-155° C.

EXAMPLE 28 Preparation ofmethyl[3-(2'-chloro-6'-fluorobenzylidene)]-carbazate

One proceeds in the way described in Example 1 with the difference that47.65 g (0.3 moles) of 2-chloro-6-fluorobenzaldehyde and 27 g (0.3moles) of methyl carbazate are used as the starting substances. 45 g(65.2%) of the title compound are obtained. M.p. 152°-153° C.

EXAMPLE 29

A premix for supplementing pig fodder is prepared with the followingcomposition:

    ______________________________________                                        Components            Amounts                                                 ______________________________________                                        Vitamin A             3,000,000  IU                                           Vitamin D.sub.3       600,000    IU                                           Vitamin E             4,000      IU                                           Vitamin K.sub.3       400        mg                                           Vitamin B.sub.1       600        mg                                           Vitamin B.sub.2       800        mg                                           Vitamin B.sub.3       2,000      mg                                           Vitamin B.sub.6       800        mg                                           Vitamin B.sub.12      10         mg                                           Niacine               4,000      mg                                           Choline chloride      60,000     mg                                           Active agent according to Example 7                                                                 10,000     mg                                           Butylhydroxytoluene (antioxidant)                                                                   30,000     mg                                           Flavoring substances  8,000      mg                                           Sodium saccharate     30,000     mg                                           Trace elements:                                                               Mn                    8,000      mg                                           Fe                    30,000     mg                                           Zn                    20,000     mg                                           Cu                    6,000      mg                                           I                     100        mg                                           Twice-ground bran ad  1,000      g                                            ______________________________________                                    

This premix of vitamins and trace elements is admixed with the basalfodder in a concentration of 0.5 kg per 100 kg.

EXAMPLE 30

A premix for supplementing piglet fodder is prepared with the followingcomposition:

    ______________________________________                                        Components            Amounts                                                 ______________________________________                                        Vitamin A             1,200,000  IU                                           Vitamin D.sub.3       300,000    IU                                           Vitamin B             2,000      IU                                           Vitamin B.sub.2       600        mg                                           Vitamin B.sub.3       2,000      mg                                           Vitamin B.sub.12      5          mg                                           Niacine               3,000      mg                                           Choline chloride      40,000     mg                                           Active agent according to Example 7                                                                 10,000     mg                                           Butylhydroxytoluene (antioxidant)                                                                   30,000     mg                                           Trace elements:                                                               Mn                    6,000      mg                                           Fe                    10,000     mg                                           Zn                    15,000     mg                                           Cu                    30,000     mg                                           I                     100        mg                                           Twice-ground bran ad  1,000      g                                            ______________________________________                                    

This premix of vitamins and trace elements is admixed with the basalfodder in a concentration of 0.5 kg per 100 kg.

EXAMPLE 31

0.5 kg of a premix as described in Example 21 are admixed with 100.0 kgof a basal fodder with the following composition:

    ______________________________________                                        Components           Amounts, kg                                              ______________________________________                                        Maize                37.6                                                     Barley               25.4                                                     Wheat                6.0                                                      Oats                 5.0                                                      Soybean              13.0                                                     Fish meal            6.0                                                      Bran                 2.4                                                      Fat powder           1.5                                                      Premix of minerals.sup.x                                                                           1.0                                                      Lime (fodder quality)                                                                              1.0                                                      Sodium chloride (fodder quality)                                                                   0.5                                                      Biolisine            0.1                                                      Premix according to Example 21                                                                     0.5                                                      Total weight:        100.0 kg                                                 ______________________________________                                    

The active agent content of the resulting pig fodder is 50 ppm.

^(x) The composition of the premix of minerals is as follows:

    ______________________________________                                        Components        Amounts, %                                                  ______________________________________                                        Dicalcium phosphate                                                                             55.0                                                        Monocalcium phosphate                                                                           40.0                                                        Calcium carbonate  5.0                                                        ______________________________________                                    

EXAMPLE 32

0.5 kg of a premix as described in Example 30 are admixed with 100.0 kgof a basal fodder with the following composition:

    ______________________________________                                        Components             Amounts, kg                                            ______________________________________                                        Maize                  25.0                                                   Wheat                  34.0                                                   Extracted soybean      18.0                                                   Milk powder            9.9                                                    Fish meal              4.0                                                    Yeast (fodder quality) 2.0                                                    Fat powder             3.4                                                    Premix of minerals according to Example 23                                                           1.8                                                    Lime (fodder quality)  1.0                                                    Sodium chloride (fodder quality)                                                                     0.4                                                    Premix according to Example 22                                                                       0.5                                                    Total weight:          100.0 kg                                               ______________________________________                                    

The active agent content of the resulting piglet fodder is 50 ppm.

EXAMPLE 33

400 kg of a pre-ground soybean meal are filled into a mixer, 3.1 kg ofsoybean oil are added under stirring, and the mixture is stirred untilthe solids are coated with oil. Thereafter 9.1 kg of an active agentaccording to Example 4 are added and the mixture is stirred until ahomogeneous blend is obtained. Finally 9.0 kg of soybean oil are added,and the mixture is homogenized again.

EXAMPLE 34

0.5 kg of an active agent according to Example 4 are added to 40 kg ofcorn mean under stirring, and simultaneously 3.0 kg of propylene glycolare sprayed into the mixture. Thereafter 1.4 kg of dicalcium phosphateare added and the mixture is homogenized.

EXAMPLE 25

10 kg of alfalfa meal and 15 kg of VEPEX® are stirred for 20 hours,thereafter 1 kg of maize oil is started to spray into the mixture withan even speed so that spraying is continued during the introduction ofthe following additional components: 2.5 kg of an active agent accordingto Example 4, 10 kg of maize starch, 2.5 kg of the above active agent0.3 kg of silicon dioxide, 0.6 kg of ascorbic acid, 9 kg of maize starchand 2.5 kg of the above active agent. Thereafter the mixture is stirredfor an additional 5 minutes.

EXAMPLE 36

One proceeds as described in Example 33 with the difference thatbutylene glycol is applied as wetting agent instead of soybean oil.

EXAMPLE 37

(A) 3.5 kg of potato starch are admixed with 2.9 kg of an active agentaccording to Example 1. 0.05 kg of mineral oil are sprayed into themixture, thereafter 0.2 kg of sorbic acid, 0.4 kg of silicon dioxide and0.1 kg of calcium propionate are added, and the mixture is stirred foran additional 2 minutes.

(B) 4.2 kg of fish meal are admixed with 22 kg of rye bran, 0.6 kg ofmineral oil are sprayed into the mixture, thereafter 4 kg of a mixtureprepared according to point (A), 10 kg of maize meal, 4 kg of a mixtureprepared according to point (A) and 9 kg of maize meal are introducedunder stirring. Finally 0.6 kg of mineral oil are sprayed into themixture.

EXAMPLE 38

100 kg of wheat bran, 10 kg of an active agent according to Example 2,2.5 kg of calcium carbonate, 0.15 kg of α-tocopherol and 0.4 kg ofcalcium propionate are homogenized with 4 kg of propylene glycol.

EXAMPLE 39

10 kg of soybean meal and 0.6 kg of an active agent according to Example3 are homogenized with 2.5 kg of butylene glycol.

EXAMPLE 40

50 kg of soybean meal, 6 kg of an active agent according to Example 5,0.5 of silicon dioxide and 0.2 kg of calcium propionate are homogenizedwith 1.6 kg of soybean oil.

We claim:
 1. An animal fodder having a weight gain increasing effectwhich comprises as active ingredient effective to cause weight gain inan animal in an amount of 1 ppm to 85% by weight a compound of theFormula I

    R.sup.1 ═N--NH--COOR.sup.3                             (I)

wherein R¹ stands for a C₇ -C₁₂ cycloalkylidene group, an indanylidenegroup, or a group of the Formula (IX) ##STR5## wherein A is a phenylgroup which can have one or more identical or different substituentsselected from the group consisting of halo, nitro, hydroxy, C₁ -C₄alkoxy, C₁ -C₄ alkyl, amino, and C₁ -C₄ alkoxycarbonyl-hydrazino; or Ais phenyl-(C₁ -C₄ alkyl), C₁ -C₁₆ alkyl, C₃ -C₇ cycloalkyl, indolyl, ora C₃ -C₆ cycloalkyl group substituted by C₃ -C₆ cycloalkyl; R² ishydrogen, C₁ -C₆ alkyl, or C₃ -C₇ cycloalkyl; and R³ is C₁ -C₄ alkyl, ora biologically acceptable salt thereof in admixture with an edible solidor liquid carrier or diluent suitable for use in animal husbandry andwith an additive generally used in the production of fodders.
 2. Theanimal fodder defined in claim 1 wherein the edible solid or liquiddiluent suitable for use in animal husbandry is selected from the groupconsisting of wheat, rice, corn, soybeans, alfalfa, barley, oats, rye,each in a form appropriate for an animal fodder, fish meal, meat meal,bone meal, and mixtures thereof.
 3. The animal fodder defined in claim 1wherein the additive generally used in the production of fodders is awetting agent or an antioxidant.
 4. The animal fodder defined in claim 1further comprising vitamins and trace elements conventionally added tofodders.
 5. The animal fodder defined in claim 1 in the form of of aconcentrate which contains the compound of the formula (I) in an amountof 5 to 80% by weight.
 6. The animal fodder defined in claim 1 in a formready for use which contains 1 to 400 ppm of the compound of the formula(I).
 7. A method for improving the weight gain and fodder utilization ofanimals which comprises the step of feeding said animals with a fodderaccording to claim
 1. 8. An animal fodder having a weight gainincreasing effect which comprises an active ingredient effective tocause weight gain in an animal in an amount of 1 ppm to 85% by weight acompound selected from the group consistingof:methyl-(3-cyclohexylidene)-carbazate andmethyl[3-(2'-cyclohexylcyclohexylidene)]-carbazate;or a biologicallyacceptable salt thereof in admixture with an edible solid or liquidcarrier or diluent suitable for use in animal husbandry and with anadditive generally used in the preparation of fodders.
 9. A method forimproving the weight gain and fodder utilization of animals whichcomprises the step of feeding said animals with a fodder according toclaim 8.